biostudies-literatureOdera DONational Institute for Health Research (NIHR)Wellcome Trusteabn5993https://www.ebi.ac.uk/biostudies/studies/S-EPMC7616656biostudies-literatureUnknown15(682)Natural killer (NK) cells are potent immune effectors that can be activated via antibody-mediated Fc receptor engagement. Using multiparameter flow cytometry, we found that NK cells degranulate and release IFN-γ upon stimulation with antibody-opsonized <i>Plasmodium falciparum</i> merozoites. Antibody-dependent NK (Ab-NK) activity was largely strain transcending and enhanced invasion inhibition into erythrocytes. Ab-NK was associated with the successful control of parasitemia after experimental malaria challenge in African adults. In an independent cohort study in children, Ab-NK increased with age, was boosted by concurrent <i>P. falciparum</i> infections, and was associated with a lower risk of clinical episodes of malaria. Nine of the 14 vaccine candidates tested induced Ab-NK, including some less well-characterized antigens: P41, P113, MSP11, RHOPH3, and <i>Pf</i>_11363200. These data highlight an important role of Ab-NK activity in immunity against malaria and provide a potential mechanism for evaluating vaccine candidates.Science translational medicineAnti-merozoite antibodies induce natural killer cell effector function and are associated with immunity against malaria.PMC761665616/136/33107499Mwai KDiehl SBejon PRosenkranz MOoko MWinterberg MOsier FHAKamuya DKapulu MCKivisi COgutu BLowe BHoffman SLBillingsley PFNgoto OKimathi Rde Laurent ZKibinge NMusasia FKFrank RNgoi JMBull PCMuthui MNyangweso GOmuoyo DTuju JAudi AChi PCOngas MOKoskei NShangala JOdera DOWilliams TNMusembi JOngecha JOtieno EMurungi LMarsh KCHMI-SIKA Study TeamMusyoki JRichie TLJames ERKamuyu GNjue MKimani DKinyanjui SMwacharo JMohammed KSMarsh VKariuki SMosobo MFurle KMwongeli JSim BKLNjuguna PTarning JImwong MJao IOlewe FAbdi AIChege TWambua JMurphy SCAbebe YMwanga DNdungu FOloo JHodgson SHNkumama INMakale JHamaluba MfalseAnti-merozoite antibodies induce natural killer cell effector function and are associated with immunity against malaria.Natural killer (NK) cells are potent immune effectors that can be activated via antibody-mediated Fc receptor engagement. Using multiparameter flow cytometry, we found that NK cells degranulate and release IFN-γ upon stimulation with antibody-opsonized <i>Plasmodium falciparum</i> merozoites. Antibody-dependent NK (Ab-NK) activity was largely strain transcending and enhanced invasion inhibition into erythrocytes. Ab-NK was associated with the successful control of parasitemia after experimental malaria challenge in African adults. In an independent cohort study in children, Ab-NK increased with age, was boosted by concurrent <i>P. falciparum</i> infections, and was associated with a lower risk of clinical episodes of malaria. Nine of the 14 vaccine candidates tested induced Ab-NK, including some less well-characterized antigens: P41, P113, MSP11, RHOPH3, and <i>Pf</i>_11363200. These data highlight an important role of Ab-NK activity in immunity against malaria and provide a potential mechanism for evaluating vaccine candidates.2023-01-01T00:00:00Z2023 Feb2026-06-07T08:14:38.991Z2025-04-04T23:49:58.374ZS-EPMC76166563675356110.1126/scitranslmed.abn5993